Dr. Cheryl Rosenfeld, the applicant, has a D.V.M. (University of Illinois, Urbana-Champaign 1995) and two years of Anatomical Pathology residency training at Missouri. She then completed a Ph.D. in Animal Sciences with Dr. Dennis Lubahn on abnormalities in the ovaries and reproductive tract of mice null for the estrogen receptor-alpha gene (ERaKO mouse). She is currently a Research Assistant Professor with her sponsor for this proposal, Dr. R. Michael Roberts, a Curators' Professor at Missouri and member of the National Academy of Sciences. Dr. Roberts' interests are maternal recognition of pregnancy and particularly in the role that is played by Type I interferons (IFNs) in early pregnancy of the large farm mammals. Dr. Rosenfeld has been studying the structure and distribution of IFN receptor subunits within the uterus of the sheep as her primary project. She currently has a 25% commitment as an instructor in Veterinary Microanatomy. Dr. Rosenfeld is the first author on seven refereed papers and a co-author on eight more. Her goal is to obtain a tenure track faculty position that will allow her to conduct teaching and research in cancer biology and comparative medicine. The hypothesis that underpins this proposal is that Type I IFN transcriptionally up-regulate the activity of the estrogen receptor-beta (ERbeta) gene in endometrium, which in turn modulates the concentration of the estrogen receptor-alpha (ERa). The overall objective of these experiments is to prove this hypothesis and determine whether type I IFN, either alone or in combination with an anti-estrogen, have any potential for treating human uterine cancers. The work will involve a study of effects on cell proliferation and apoptosis and on the regulation or ERa and ERb in cells derived from endometrial cancers, experiments to determine the transcriptional control of ERb expression, and microarray experiments to compare the effects of IFN on gene expression in the uteri of mice null for either ERa or ERb. All of this work is transferable when Dr. Rosenfeld takes a permanent position. The University of Missouri has an outstanding program in reproductive biology, with faculty working in cancer biology and endocrine disruption, as well as biochemical endocrinology and genetics. The University is in the process of developing a Comparative Oncology Program. The campus provides a rich mix of disciplines and a collaborative environment, in which Dr. Rosenfeld is expected to continue to thrive.